Isotopic labeling of DNA in rat adipose tissue: evidence for proliferating cells associated with mature adipocytes.

Klyde, Barry J.; Hirsch, Jules

doi:10.1016/s0022-2275(20)40023-9

“…Studies in rodents and humans employing diverse methodologies including radiolabeling, stable isotope labeling, 14 C birth-dating, and genetic lineage tracing, collectively demonstrate ongoing formation of new adipocytes in adult AT (5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

A Cycle of Inflammatory Adipocyte Death and Regeneration in Murine Adipose Tissue

Monji

¹

,

Zhang

²

,

Kumar

³

et al. 2022

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Adipose tissue (AT) expands by a combination of two fundamental cellular mechanisms: hypertrophic growth of existing adipocytes or through generation of new adipocytes also known as hyperplastic growth. Multiple lines of evidence suggest a limited capacity for hyperplastic growth of adipose tissue in adulthood and that adipocyte number is relatively stable even with fluctuations in AT mass. If adipocyte number is stable in adulthood, despite well-documented birth and death of adipocytes, then this would suggest that birth may be coupled to death in a regenerative cycle. To test this hypothesis, we examined the dynamics of birth of new fat cells in relationship to adipocyte death, using high fidelity stable isotope tracer methods in C57Bl6 mice. We discovered birth of new adipocytes at higher frequency in histological proximity to dead adipocytes. In diet-induced obesity, adipogenesis surged after an adipocyte death peak beyond 8 weeks of high fat feeding. Through transcriptional analyses of adipose tissue and fractionated adipocytes, we found that the dominant cell death signals were inflammasome-related. Pro-inflammatory signals were particularly evident in hypertrophied adipocytes or with deletion of a constitutive oxygen sensor and inhibitor of Hypoxia inducible factor (HIF), Egln1. We leveraged the potential role for the inflammasome in adipocyte death to test the adipocyte death-birth hypothesis, finding that Caspase 1 loss of function attenuated adipocyte death and birth in murine visceral adipose tissue. These data collectively point to a regenerative cycle of adipocyte death and birth as a driver of adipogenesis in adult murine adipose tissue.

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“…Studies in rodents and humans employing diverse methodologies including radiolabeling, stable isotope labeling, 14 C birth-dating, and genetic lineage tracing, collectively demonstrate ongoing formation of new adipocytes in adult AT (5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

A cycle of inflammatory adipocyte death and regeneration in murine adipose tissue

Admin¹,

Monji²,

Zhang³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

Adipose tissue (AT) expands by a combination of two fundamental cellular mechanisms: hypertrophic growth of existing adipocytes or through generation of new adipocytes also known as hyperplastic growth. Multiple lines of evidence suggest a limited capacity for hyperplastic growth of adipose tissue in adulthood and that adipocyte number is relatively stable even with fluctuations in AT mass. If adipocyte number is stable in adulthood, despite well-documented birth and death of adipocytes, then this would suggest that birth may be coupled to death in a regenerative cycle. To test this hypothesis, we examined the dynamics of birth of new fat cells in relationship to adipocyte death, using high fidelity stable isotope tracer methods in C57Bl6 mice. We discovered birth of new adipocytes at higher frequency in histological proximity to dead adipocytes. In diet-induced obesity, adipogenesis surged after an adipocyte death peak beyond 8 weeks of high fat feeding. Through transcriptional analyses of adipose tissue and fractionated adipocytes, we found that the dominant cell death signals were inflammasome-related. Pro-inflammatory signals were particularly evident in hypertrophied adipocytes or with deletion of a constitutive oxygen sensor and inhibitor of Hypoxia inducible factor (HIF), Egln1. We leveraged the potential role for the inflammasome in adipocyte death to test the adipocyte death-birth hypothesis, finding that Caspase 1 loss of function attenuated adipocyte death and birth in murine visceral adipose tissue. These data collectively point to a regenerative cycle of adipocyte death and birth as a driver of adipogenesis in adult murine adipose tissue.

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“…Obesity increases the risk for many diseases, including cardiovascular disease, stroke, type 2 diabetes, physical disability ( 4 , 5 ), and cancer ( 6 ). The cellular basis of obesity involves an increased number and size of adipocytes, resulting from proliferation and differentiation of adipocyte progenitor cells or preadipocytes ( 7 , 8 ). Adipocytes contribute more than 90% of the adipose tissue volume in the human body and other vertebral animals ( 9 ).…”

mentioning

confidence: 99%

Hop2 interacts with the transcription factor CEBPα and suppresses adipocyte differentiation

Lin

¹

,

Zhang

²

,

Zhang

³

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Isotopic labeling of DNA in rat adipose tissue: evidence for proliferating cells associated with mature adipocytes.

Cited by 65 publications

References 24 publications

A Cycle of Inflammatory Adipocyte Death and Regeneration in Murine Adipose Tissue

A Cycle of Inflammatory Adipocyte Death and Regeneration in Murine Adipose Tissue

A cycle of inflammatory adipocyte death and regeneration in murine adipose tissue

Hop2 interacts with the transcription factor CEBPα and suppresses adipocyte differentiation

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